The overall goal of the Neurological Emergencies Treatment Trials (NETT) Network is to improve the outcomes of patients with acute neurological illness and injury by identifying effective treatments given in the earliest stages of care. In developing the NETT, the NINDS recognized that pre-clinical and translational research has demonstrated that there is a very narrow window of opportunity in which novel treatments for neurological emergencies are optimally effective, and that conducting research in the emergency setting presents unique pragmatic challenges to clinical investigators. Over the past four years, the NETT has proven to be a platform capable of selecting, developing, and simultaneously conducting multiple confirmatory clinical trials of very early interventions delivered in the ambulance or the emergency department (ED). The NETT has successfully competed for funding and implemented four actively enrolling clinical trials, two of which utilize exception from informed consent (EFIC), and one of which is already nearing completion. Several other trials are being developed with investigators from within as well as outside of the NETT. In all the trials initiated in NETT, subject accrual has been ahead of expectations and on budget. The successful operation can be attributed to the efficiency of the NETT organization and processes. The coordinating activities of the NETT are supported by two NINDS cooperative agreement grants to the Clinical Coordinating Center (CCC) at the University of Michigan (U01 NS056975) and the Statistical and Data Management Center (SDMC) in the Division of Biostatistics and Epidemiology (DBE) at the Medical University of South Carolina (U01 NS059041). In addition, 17 academic centers (Hubs) participate in the NETT with R01 grant support to each center from the NINDS. For the second five-year grant period, the CCC's aims are to maintain and enhance the collaborative relationships that form the NETT, develop trials that address important clinical questions, effectively disseminate and translate our findings, and continue to provide efficient project management for clinical trials to be conducted by the NETT. We will also explore innovations in clinical trial designs including adaptive study designs.